Exosomes derived from SW480 colorectal cancer cells promote cell migration in HepG2 hepatocellular cancer cells via the mitogen-activated protein kinase pathway

Chiba,Mitsuru; Watanabe,Narumi; Watanabe,Miki; Sakamoto,Maki; Sato,Akika; Fujisaki,Mizuki; Kubota,Shiori; Monzen,Satoru; Maruyama,Atsushi; Nanashima,Naoki; Kashiwakura,Ikuo; Nakamura,Toshiya

doi:10.3892/ijo.2015.3255

Exosomes derived from SW480 colorectal cancer cells promote cell migration in HepG2 hepatocellular cancer cells via the mitogen-activated protein kinase pathway

Authors:
- Mitsuru Chiba
- Narumi Watanabe
- Miki Watanabe
- Maki Sakamoto
- Akika Sato
- Mizuki Fujisaki
- Shiori Kubota
- Satoru Monzen
- Atsushi Maruyama
- Naoki Nanashima
- Ikuo Kashiwakura
- Toshiya Nakamura
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Affiliations: Department of Biomedical Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan, Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan, Research Center for Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan, Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
Published online on: November 19, 2015 https://doi.org/10.3892/ijo.2015.3255
Pages: 305-312

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Abstract

Exosomes are membrane-derived extracellular vesicles that have recently been recognized as important mediators of intercellular communication. In the present study, we investigated the effects of exosomes derived from SW480 colorectal cancer cells in recipient HepG2 hepatocellular cancer cells. We demonstrated that SW480-derived exosomes were taken up by the recipient HepG2 cells via dynamin-dependent endocytosis and were localized to the HepG2 lysosomes. In addition, SW480-derived exosomes induced the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 following their uptake into HepG2 cells. Of note, these changes occurred during the early phase after exosome treatment. Furthermore, SW480-derived exosomes promoted the migration of recipient HepG2 cells in a wound-healing assay, which was suppressed by pretreatment with U0126, an upstream inhibitor of ERK1/2. These results indicated that SW480-derived exosomes activated a classical mitogen-activated protein kinase pathway in recipient HepG2 cells via dynamin-dependent endocytosis and subsequently enhanced cell migration by ERK1/2 activation. Our results provide new insights into the regulation of cellular functions by exosomes.

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